title: Understanding placebo responses in Alzheimer's disease clinical trials from the literature meta-data and CAMD database.
abstract: BACKGROUND
  The placebo response and the underlying disease progression is difficult to differentiate in longitudinal Alzheimer's disease (AD) studies, yet it is crucial to understand for designing clinical trials and interpreting results.
  
  
  OBJECTIVE
  The placebo response in ADAS-cog11 from various studies was evaluated against model predictions derived from historical placebo data to demonstrate potential interpretation of study results using a prior understanding of expected disease progression.
  
  
  METHODS
  The placebo response component from a previously published disease progression model was used to estimate the longitudinal placebo response, and the disease progression in the placebo group in various case studies were evaluated. In addition, placebo data from the Coalition Against Major Diseases (CAMD) database in mild to moderate AD patients is described.
  
  
  RESULTS
  The case studies demonstrated potential different results in disease progression in a placebo group, and the impact on understanding the magnitude of drug effect. Baseline cognitive function is an important covariate of disease progression, therefore, it is important to evaluate the baseline severity and predict disease progression accordingly when comparing trial results. Furthermore, study duration, sample size, and study design may affect the placebo response, all of which have the potential to confound understanding of study results.
  
  
  CONCLUSIONS
  The recent failures in Phase III AD studies are not likely due to insufficient cognitive decline in the control groups. A meta-analytic approach using all available data provides a robust understanding of placebo effect, disease progression, and potential interpretation of treatment effects, and offers a useful tool to aid in both trial design and interpretation.
authors.affiliation: Pfizer Inc., Groton, CT 06340, USA. Kaori.Ito@pfizer.com
authors.forename: Kaori
authors.initials: K
authors.lastname: Ito
authors.forename: Brian
authors.initials: B
authors.lastname: Corrigan
authors.forename: Klaus
authors.initials: K
authors.lastname: Romero
authors.forename: Richard
authors.initials: R
authors.lastname: Anziano
authors.forename: Jon
authors.initials: J
authors.lastname: Neville
authors.forename: Diane
authors.initials: D
authors.lastname: Stephenson
authors.forename: Richard
authors.initials: R
authors.lastname: Lalonde
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000379:methods / Q000639:trends; D032882:Comprehension; D016208:Databases, Factual / Q000639:trends; D006801:Humans; D015990:Placebo Effect